The proposed research will investigate biological and psychological characteristics which distinguish persons who develop dementia in old age from those who do not. The study is designed to test the following hypotheses: 1) Patients diagnosed as having Alzheimer type dementia (DAT) have a higher frequency of cytogenetic and/or immunologic changes than patients with multi-infarct dementia (MID) or Major Depressive Disorder, or controls, 2) Psychometric profiles of DAT patients differ significantly from profiles of persons with Major Depressive Disorder or controls but not from those of MID patients. 3) Some first-degree relatives of DAT patients have the specified changes in biological phenotypes characterizing DAT patients, while others do not. 4) Relatives showing biological changes similar to those of DAT patients are at increased risk of developing DAT. 5) Relatives at risk for DAT show premorbid psychological changes distinguishing them from other relatives. An integrated psychobiological investigation of DAT is planned, utilizing a family study methodology. First, a group of subjects with idiopathic dementia (principally DAT but also some MID and mixed types) will be studied and compared to patients with Major Depressive Disorder, and to controls, to identify biological, psychiatric, and psychological correlates unique to DAT. Secondly, first-degree relatives will be studied to identify those individuals who share the characteristics of the probands and who may be at increased risk of developing DAT. Thus, the proposed research on Alzheimer type dementia will permit an intensive evaluation of biological and psychosocial variables, and their relationship to intellectual functioning, in patients with this disease. Further, the study may permit the identification of individuals at increased risk for developing dementia; and it may shed light on factors important in the etiology and pathogenesis of this major disorder and point to strategies of prevention and intervention.